AL1A1_MACFA
ID AL1A1_MACFA Reviewed; 501 AA.
AC Q8HYE4;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Aldehyde dehydrogenase 1A1 {ECO:0000305|PubMed:12576512};
DE EC=1.2.1.19 {ECO:0000250|UniProtKB:P24549};
DE EC=1.2.1.28 {ECO:0000250|UniProtKB:P00352};
DE EC=1.2.1.3 {ECO:0000269|PubMed:12576512};
DE EC=1.2.1.36 {ECO:0000269|PubMed:12576512};
DE AltName: Full=3-deoxyglucosone dehydrogenase {ECO:0000250|UniProtKB:P00352};
DE AltName: Full=ALDH-E1;
DE AltName: Full=ALHDII;
DE AltName: Full=Aldehyde dehydrogenase family 1 member A1;
DE AltName: Full=Aldehyde dehydrogenase, cytosolic {ECO:0000305};
DE AltName: Full=Retinal dehydrogenase 1 {ECO:0000303|PubMed:12576512};
DE Short=RALDH 1 {ECO:0000303|PubMed:12576512};
DE Short=RalDH1 {ECO:0000303|PubMed:12576512};
GN Name=ALDH1A1 {ECO:0000250|UniProtKB:P00352};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC TISSUE=Kidney proximal tubule;
RX PubMed=12576512; DOI=10.1194/jlr.m200359-jlr200;
RA Brodeur H., Gagnon I., Mader S., Bhat P.V.;
RT "Cloning of monkey RALDH1 and characterization of retinoid metabolism in
RT monkey kidney proximal tubule cells.";
RL J. Lipid Res. 44:303-313(2003).
CC -!- FUNCTION: Cytosolic dehydrogenase that catalyzes the irreversible
CC oxidation of a wide range of aldehydes to their corresponding
CC carboxylic acid (PubMed:12576512). Functions downstream of retinol
CC dehydrogenases and catalyzes the oxidation of retinaldehyde into
CC retinoic acid, the second step in the oxidation of retinol/vitamin A
CC into retinoic acid (PubMed:12576512). This pathway is crucial to
CC control the levels of retinol and retinoic acid, two important
CC molecules which excess can be teratogenic and cytotoxic (Probable).
CC Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-
CC hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein
CC adducts and are highly cytotoxic. By participating for instance to the
CC clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium
CC prevents the formation of HNE-protein adducts and lens opacification.
CC Functions also downstream of fructosamine-3-kinase in the fructosamine
CC degradation pathway by catalyzing the oxidation of 3-deoxyglucosone,
CC the carbohydrate product of fructosamine 3-phosphate decomposition,
CC which is itself a potent glycating agent that may react with lysine and
CC arginine side-chains of proteins (By similarity). Has also an
CC aminobutyraldehyde dehydrogenase activity and is probably part of an
CC alternative pathway for the biosynthesis of GABA/4-aminobutanoate in
CC midbrain, thereby playing a role in GABAergic synaptic transmission (By
CC similarity). {ECO:0000250|UniProtKB:P00352,
CC ECO:0000250|UniProtKB:P24549, ECO:0000269|PubMed:12576512,
CC ECO:0000305|PubMed:12576512}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC Evidence={ECO:0000269|PubMed:12576512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186;
CC Evidence={ECO:0000305|PubMed:12576512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinal + H2O + NAD(+) = all-trans-retinoate + 2
CC H(+) + NADH; Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36;
CC Evidence={ECO:0000269|PubMed:12576512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081;
CC Evidence={ECO:0000305|PubMed:12576512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinal + H2O + NAD(+) = 9-cis-retinoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:42084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78273,
CC ChEBI:CHEBI:78630; Evidence={ECO:0000269|PubMed:12576512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42085;
CC Evidence={ECO:0000305|PubMed:12576512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinal + H2O + NAD(+) = 11-cis-retinoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:47132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16066, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:87435; Evidence={ECO:0000250|UniProtKB:P51647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13-cis-retinal + H2O + NAD(+) = 13-cis-retinoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:67332, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:169952; Evidence={ECO:0000269|PubMed:12576512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67333;
CC Evidence={ECO:0000305|PubMed:12576512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-deoxyglucosone + H2O + NAD(+) = 2-dehydro-3-deoxy-D-
CC gluconate + 2 H(+) + NADH; Xref=Rhea:RHEA:67244, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:57990, ChEBI:CHEBI:60777;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67245;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-4-hydroxynon-2-enal + H2O + NAD(+) = (E)-4-hydroxynon-2-
CC enoate + 2 H(+) + NADH; Xref=Rhea:RHEA:67248, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58968, ChEBI:CHEBI:142920;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + malonaldehyde + NAD(+) = 3-oxopropanoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:67252, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33190, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:566274; Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67253;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexanal + NAD(+) = 2 H(+) + hexanoate + NADH;
CC Xref=Rhea:RHEA:67276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17120, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:88528; Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + propanal = 2 H(+) + NADH + propanoate;
CC Xref=Rhea:RHEA:67256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17153, ChEBI:CHEBI:17272, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetaldehyde + H2O + NAD(+) = acetate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:25294, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25295;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=benzaldehyde + H2O + NAD(+) = benzoate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:11840, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16150, ChEBI:CHEBI:17169, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.28;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11841;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-aminobutanal + H2O + NAD(+) = 4-aminobutanoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:19105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58264,
CC ChEBI:CHEBI:59888; EC=1.2.1.19;
CC Evidence={ECO:0000250|UniProtKB:P24549};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106;
CC Evidence={ECO:0000250|UniProtKB:P24549};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.21 uM for all-trans retinal (at pH 7.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:12576512};
CC KM=2.63 uM for 9-cis retinal (at pH 7.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:12576512};
CC KM=1.51 uM for 13-cis retinal (at pH 7.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:12576512};
CC Vmax=14.08 nmol/min/mg enzyme with all-trans retinal (at pH 7.5 and
CC 25 degrees Celsius) {ECO:0000269|PubMed:12576512};
CC Vmax=24.15 nmol/min/mg enzyme with 9-cis retinal (at pH 7.5 and 25
CC degrees Celsius) {ECO:0000269|PubMed:12576512};
CC Vmax=9.35 nmol/min/mg enzyme with 13-cis retinal (at pH 7.5 and 25
CC degrees Celsius) {ECO:0000269|PubMed:12576512};
CC Note=Has a nearly 2-fold higher catalytic efficiency for 9-cis
CC retinal compared to all-trans and 13-cis retinal.
CC {ECO:0000269|PubMed:12576512};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:12576512};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:12576512}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with PRMT3; the
CC interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity
CC and is independent of the methyltransferase activity of PRMT3 (By
CC similarity). {ECO:0000250|UniProtKB:P00352,
CC ECO:0000250|UniProtKB:P51977}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P00352}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P24549}.
CC -!- PTM: The N-terminus is blocked most probably by acetylation.
CC {ECO:0000250|UniProtKB:P15437}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF542418; AAN85861.1; -; mRNA.
DR AlphaFoldDB; Q8HYE4; -.
DR SMR; Q8HYE4; -.
DR STRING; 9541.XP_005581989.1; -.
DR eggNOG; KOG2450; Eukaryota.
DR UniPathway; UPA00912; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0106373; F:3-deoxyglucosone dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:RHEA.
DR GO; GO:0001758; F:retinal dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; ISS:UniProtKB.
DR GO; GO:0030392; P:fructosamine catabolic process; ISS:UniProtKB.
DR GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0036438; P:maintenance of lens transparency; ISS:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS_CYS.
DR InterPro; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Cytoplasm; Lipid metabolism; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P15437"
FT CHAIN 2..501
FT /note="Aldehyde dehydrogenase 1A1"
FT /id="PRO_0000056416"
FT REGION 336..501
FT /note="Mediates interaction with PRMT3"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT ACT_SITE 269
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 303
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 167..170
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 193..196
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 226..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 246..247
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 269..271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 349..353
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 400..402
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT SITE 170
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P15437"
FT MOD_RES 91
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 367
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 410
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 419
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 495
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
SQ SEQUENCE 501 AA; 54736 MW; E3864A9190BBD6B2 CRC64;
MSSSGTSDLP VLPTDLKIQY TKIFINNEWH DSVSGKKFPV FNPATEEELC QVEEGDKADV
DKAVKAARQA FQIGSPWRTM DASERGRLLY KLADLIERDR LLLATMESMN GGKLYSNAYL
NDLAGCIKTL RYCAGWADKI QGRTIPIDGN FFTYTRHEPI GVCGQIIPWN FPLVMLIWKI
GPALSCGNTV VVKPAEQTPL TALHVASLIK EAGFPPGVVN IVPGYGPTAG AAISSHMDID
KVAFTGSTEV GKLIKEAAGK SNLKRVTLEL GGKSPCIVLA DADLDNAVEF AHHGVFYHQG
QCCIAASRIF VEESIYDEFV RRSVERAKKY ILGNPLTPGA TQGPQIDKEQ YDKILDLIES
GKKEGAKLEC GGGPWGNKGY FVQPTVFSNV TDEMRIAKEE IFGPVQQIMK FKSLDDVIKR
ANNTFYGLSA GVFTNDIDKA VTISSALQAG TVWVNCYGVV TAQCPFGGFK MSGNGRELGE
YGFHEYTEVK TVTVKISQKN S
